The Nocebo Effect: What You Hear Can Hurt You

Negative expectations about a drug can influence the occurrence and severity of side effects. Community pharmacists are in a good position to help patients who experience side effects from a drug partly because they expect to have them, which can affect their adherence.

The phenomenon, known as the nocebo effect, may be experienced by patients when a medication or a placebo is administered. The effect inadvertently conditions the individual to expect a negative response or to anticipate negative effects from a medication based on what they have heard or read about it. For example, a German study has found that patients were more inclined to report side effects from a placebo when they were told that the drug was expensive.

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If a patient expects to experience clinical pain, for instance, they actually experience it, according to Luana Colloca, MD, PhD, an Associate Professor at the University of Maryland. In an article published in the October 2017 issue of Science, Colloca and her colleagues reported that nocebo effects can influence patients’ clinical outcomes and treatment adherence in placebo-controlled clinical trials. “Nocebo responses can change a patient’s behavior. Sometimes this is a problem because it can create a negative reaction,” she said.

Daniel Mansour, PharmD, BCGP, FASCP, Interprofessional Clinical Coordinator at the Peter Lamy Center on Drug Therapy and Aging in Baltimore, stated that recent studies, including those led by Luana Colloca, MD, indicate that the nocebo effect can trigger a chain of events that has a neurobiological etiology.

“The nocebo effect derives from negative expectations and commercial features that can increase adverse events. This is especially important when a patient, particularly an older adult, is required to take a daily active medication to treat his or her disease while asymptomatic,” said Mansour in an email sent to Drug Topics.

Patients are often told that statins may cause muscle-related side effects, but the way they are told can make a difference, Mansour noted. “When inappropriately warned about the adverse drug reactions, patients may either choose to independently take a subtherapeutic dose or stop taking their statin altogether. This may lead to nonadherence and consequently cause negative clinical outcomes such as myocardial infarction and stroke. What is being related to the patient, and how, become as important as the treatment plan,” said Mansour.

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Community pharmacists, as clinicians, may need to carefully assess a patient’s treatment beliefs, and what his or her perception is in receiving prior treatments and new therapeutic plans, Mansour asserted. “Pharmacists can tailor their communication when engaging their patients and maintain a motivational demeanor in verbal and nonverbal communication when performing medication therapy management,” he said.

Nicole Brandt, PharmD, Professor at University of Maryland School of Pharmacy, said that the challenge for pharmacists is how to educate patients when they have their own perceived side effects.   

“As providers we struggle with the risk/benefit issue. They heard from friends who had an adverse event and they perceive before they even take it that they are going to have that same adverse event,” Brandt told Drug Topics.

The test for community pharmacists, said Brandt, is navigating all the potential barriers as to why patients don’t take medications including cost and perceived risk.

“We need that engagement and discussion to balance that direct to consumer ad. We want to share information, but I’m not sure that a 30-second television commercial is the ideal.”